Virus-like agents, cell wall-defective bacteria and toxic substances have been described in tissue filtrates obtained from the bowel wall of Crohn's disease patients. Recently, Crohn's disease filtrates have been processed and inoculated into athymic (nude) mice, some of which subsequently developed lymphomas. In addition, the lymphomas and splenic tissue of these mice were found to contain an antigen detectable by immunofluorescence. This antigen reacted specifically with Crohn's disease sera but not with the sera of patients with ulcerative colitis. If this work is correct, it suggests that Crohn's disease filtrates induce lymphomas in athymic mice directly or by activating an endogenous mouse virus such as a C-type virus. In addition, the immunofluorescence test, if confirmed, suggests that this may be an assay useful in differentiating Crohn's disease from ulcerative colitis since thus far, it has been specific for Crohn's disease sera. We propose to repeat this work and if successful to characterize the transmissible material and isolate the agents responsible for the development of lymphomas. We will expand the number of control tissues tested in order to determine if the induction of lymphomas is a unique effect of CD tissue, is a nonspecific effect of inflammatory tissue or represents the spontaneous development of lymphomas in athymic mice. We will expand the number of Crohn's disease and ulcerative colitis sera tested and will also test a large number of sera from patients with other diseases in order to assess the sensitivity and specificity of the immunofluorescent assay described. Since the transmissible material capable of inducing lymphomas and of inducing an antigen is presumably of human origin, the assessment and characterization of the material may provide further information regarding the pathogenesis of Crohn's disease. This may enable us to obtain more information about the causation of this disease as well as to assess the possible usefulness of a new test to differentiate Crohn's disease from ulcerative colitis and from other intestinal conditions.